An animal's gastrointestinal tract represents a surface area of vast proportions. This surface has constant contact with microorganisms and their antigens as well as receiving antigenic stimulation from foodstuffs and their digestive byproducts. The defense of the gastrointestinal tract is made much more difficult from that of the external body surfaces by having a thin epithelium, required for efficient digestion, rather than a thick integument. The lamina propria of the intestine contains large numbers of leukocytes dispersed throughout in addition to lymphoid aggregations which occur at intervals along the intestine. The milieu in which these lymphoid cells reside is so different from the environment of other parts of the body that it is conceivable that these cells have biological properties and functions which differ from those of lymphoid cells in the peripheral nodes. Indeed, evidence presently exists to support such an assertion. The proposal presented here endeavors to determine the biological and immunological properties of lamina propria and Peyer's patch lymphocytes. In particular, the nature of their humoral and cellular responsiveness to inanimate antigenic stimulation, their interrelationship with members of the normal or autochthonous intestinal flora, and the nature of their response to enteric pathogens will be studied. The effect of the intestinal flora on the development or maturation of the gut-associated lymphoid tissues will be investigated through the use of gnotobiotic as well as conventional animals.